The overall objective of this project is to characterize the role of sex in the histogenesis of chemically induced hepatocellular carcinomas using mouse model developed at the University of Chicago. The latter consists of induction of hepatocellular carcinomas following single intraperitoneal injection of diethylnitrosamine (DEN) into C57BLxC3H F1 mice. Intact mice and mice gonadectomized at different intervals following carcinogenic treatment are utilized. At 3 days after injection of DEN, all experimental mice showed hepatic fatty changes with predominant central and mid-zonal distribution. However, these changes were not present any more in mice killed 7 days after DEN treatment. The earliest focal hepatocellular changes were identified at 10 weeks following DEN treatment. The lesions, referred to as basophilic hepatocellular foci (BHF) were small (six cells in diameter) or large (up to approximately 200 cells in cross-sectional area). This basophilia was due to the accumulation of RNA, since pretreatment of sections with RNAase completely abolished their staining with toluidine blue. The number and size of BHF increased with time. Higher dose of DEN (5.00 micrograms/g body weight) induced 5-fold greater number of BHF than the lower carcinogenic dose (1.25 micrograms/g body weight). Histochemical and autoradiography data are being analyzed.